P549: ANALYSIS OF THE CLINICAL SIGNIFICANCE AND PROGNOSTIC IMPACT OF TET2 SINGLE NUCLEOTIDE POLYMORPHISM I1762V IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: Y. Li, X. Lyu
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is a malignancy that originates from myeloid hematopoietic stem/progenitor cells in the bone marrow. The currently recognized cause of AML is chromosomal abnormalities or genetic mutations in myeloid hematopoietic stem/progenitor cells induced by various physicochemical factors such as benzene, pesticides, ionizing radiation, and chemotherapeutic drugs. With the development of high-throughput sequencing technology, a variety of acquired somatic mutations are used for the diagnosis, treatment and prognostic assessment of AML. Also, genetic susceptibility due to many single nucleotide polymorphisms (SNPs) is thought to be important in the development of AML. The TET2 gene encodes a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine and contributes to the epigenetic regulation of myelopoiesis. Mutations in the TET2 gene lead to dysmethylation and myeloid transformation. The TET2 SNP I1762V (rs2454206AG/GG, c.5284A>G, p.Ile1762Val) has an allele frequency of approximately 21% in the Chinese population. Some studies have shown that pediatric AML patients carrying mutations at this locus have a better prognosis. In this study, we investigated the clinical significance of the TET2 SNP locus I1762V in AML patients and its impact on prognosis through a comprehensive analysis of high-throughput sequencing results from 413 AML patients. Aims: This study aimed to explore the clinical significance and effect on the prognosis of TET2 Single nucleotide polymorphism I1762V in patients with acute myeloid leukemia (AML). Methods: Target sequencing on 58 hematological tumor-related genes in bone marrow samples of 413 AML patients was performed using the high-throughput sequencing method. TET2 I1762V and other somatic mutations were annotated and compared with patients’ clinical information and prognosis. Results: I1762V was detected in 154 patients with AML, which was significantly different from the normal population in NyuWa Chinese Population Variant Database (χ2=72.4, P<0.001). I1762V was not related to sex, age, and karyotype of AML patients (P>0.05). The proportion of NPM1 gene mutations and KIT gene mutations in patients with I1762V was significantly higher than the others(P < 0.001). NPM1 mutations and KIT mutations were mutually exclusive. The survival analysis results showed that the OS and PFS of AML patients with I1762V were significantly higher than those of wild type patients (HR=0.55, P < 0.05), while the OS and PFS in AML patients with DNMT3A mutation (with or without I1762V mutation) were lower than those of wild type patients (HR=1.79, P < 0.05). Summary/Conclusion: TET2 SNP I1762V is an factor affecting the prognosis of AML patients, which can be used to guide the treatment and evaluate the prognosis of AML. TET2 SNP I1762V influenced the concomitant or reciprocal mutations in AML patients; I1762V was closely associated with the prognosis of AML patients. The findings demonstrate that the TET2 SNP locus I1762V is an important guide for the diagnosis, treatment and prognostic assessment of AML patients.